Sandra Loaiza - Stem Cell User Group Meeting 33, 16th June 2022 The John Goldman Centre for Cellular Therapy (JGCCT) Department of Haematology, Imperial College Healthcare NHS Trust Developing in-house, point of care manufactured chimaeric
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Sandra Loaiza - Stem Cell User Group Meeting 33, 16th June 2022 The John Goldman Centre for Cellular Therapy (JGCCT)
Department of Haematology, Imperial College Healthcare NHS Trust Developing in-house, point of care manufactured chimaeric antigen receptor (CAR)-T cells<br>
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CAR-T cell immunotherapy Established & effective treatment for relapsed/refractory B cell lineage blood cancers (ALL, lymphoma & multiple myeloma)
Currently 2 manufacturing models
High cost Low cost
Complex logistics Flexible low throughput
Lengthy process (>4 weeks) Academic / investigator led novel CAR-T cell therapies Established commercial centralised model Emerging point-of-care (POC) model<br>
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Process development
JGCCT laboratory Regulatory Portfolio
Protocol
Ethics approval
Joint Research Safety Committee approval
Investigational Medicinal Product dossier(IMPD)
Investigator’s Brochure (IB) Multi-disciplinary team
Apheresis
Manufacturing laboratory
Pharmacy
Clinical services (Haematology, Neurology & ITU) Regulatory Agencies
Joint Accreditation Committee ISCT-Europe & EBMT (JACIE)
Medicines & Healthcare Products Regulatory Agency (MHRA) What is involved in developing and implementing POC model for CAR T-cell therapy?<br>
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1st donor for in-house CAR-T manufacture with the apheresis team Flow cytometry performed on the MACSQuant® Analyzer Automated CAR-T manufacture using the CliniMACS Prodigy Instrument<br>
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CAR-T cell manufacturing using Miltenyi Biotec automated Clinimacs Prodigy system in the JGCCT laboratory d0 d12<br>
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Validation Run 1 data Panel A – cell count determination Panel B – % CAR<br>
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Validation Run 1 data Panel A – immune cell composition<br>
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Validation Run 1 data Panel B – transduction efficiency<br>
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Validation Run 1 data Summary *samples run in duplicate (above average of n=2)<br>
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Current plan at ICHNT
Process validation using healthy donors (n=3)
Apply for a variation for marketing authorisation by the MHRA
Proof of efficacy in a Phase I study in CD19+ B-cell lymphomas (n=6)
Future
Expand programme to support clinical research in autoimmune conditions such as SLE and other haematological malignancies<br>
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Establishing CAR-T cell programme at ICHNT CAR-T cell therapy falls under the ATMP framework, presenting unique challenges to all stakeholders
Joint Accreditation Committee ISCT-Europe & EBMT (JACIE) official accreditation body in haematopoietic stem cell transplantation (HSCT) and cellular therapy
Accreditation of a centre by a competent authority is understood as verification that the required standards are followed and necessary qualifications, processes and resources are present
Establishing CAR-T cell programme at ICHNT CAR-T is a complex service to deliver
Sharing of information and lessons learned by wave 1 and 2 hospitals
National CAR-T cell MDT, support from Royal Marsden
On-boarding sessions with commercial CAR-T cell companies
Pan UK Pharmacy Working Group for ATMPs<br>
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Establishing CAR-T cell programme at ICHNT Cytokine release syndrome
most common toxicity post CAR-T cell therapy, potentially life-threatening, due to immune activation release of inflammatory cytokines
Immune cell-associated neurotoxicity syndrome (ICANS)
in 20-60%, severe in 10-30%
Intensive care unit and neurology support essential
Robust SOPs and clinical guidelines/pathways
Staff training, competency assessments<br>
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Summary Phase I study in CD19+ B-cell lymphomas currently in set up with a successful validation run
Clinical preparedness, guidelines/SOPs, staff training and JACIE accreditation underway
Academia will continue to play a significant role in development and
delivery of these new therapies
Expand programme to support clinical research in autoimmune conditions such as SLE and other haematological malignancies<br>
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JGCCT Laboratory
Edward Aina
Shab Uddin
Sandra Loaiza
Emma Bray
Kaivalya Kulkarni
Robert Chisnall
Simi Fadipe
Kishmeet Kaur
Ruth Emhazion Acknowledgement Haematology Department
Anastasios Karadimitris
Jane Apperley
Lucy Cook
Renuka Palanicawandar
Eduardo Olavarria
Pharmacy staff
Apheresis Unit staff
Quality Team
Anna Bara (Imperial College) Miltenyi Biotec Technical team<br>
